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Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island.
Open accessAbstract
In an attempt to find the mechanism by which CpG islands remain free of methylation we have undertaken a detailed examination of the mouse adenine phosphoribosyltransferase (aprt) gene. This housekeeping gene has a CpG island that extends over the gene promoter and includes the first two exons. We show that the island is free of methylation at all CpGs, whereas the flanks are methyated. Detailed patterns of methylation beyond the boundaries of the CpG island vary between cells. In vivo footprinting across the island region shows that three GC boxes clustered at the 5' edge of the CpG island are occupied, most probably by Sp1. No other footprints are detected within the island region. Deletion or mutagenesis of the Sp1 sites causes de novo methylation of the CpG island in a transgenic mouse assay. Thus, the peripherally located Sp1 sites are necessary to keep the aprt island methylation free.
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Cites
CpG-rich islands and the function of DNA methylation
Bird, A. P. (1986) · Nature · doi:10.1038/321209a0 · Cited by 3,777
Self-citationHöller, M., Westin, G., Jiricny, J., & Schaffner, W. (1988) · Genes & Development · doi:10.1101/gad.2.9.1127 · Cited by 305
Cited by
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
Self-citationJaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325
Self-citationDNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906
CpG islands and the regulation of transcription
Deaton, A. M., & Bird, A. (2011) · Genes & Development · doi:10.1101/gad.2037511 · Cited by 3,187
Self-citationEpigenetic Reprogramming in Mammalian Development
Reik, W., Dean, W., & Walter, J. (2001) · Science · doi:10.1126/science.1063443 · Cited by 3,078
Metadata
- Authors
- Macleod, D., Charlton, J., Mullins, J., & Bird, A. P.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-10-01
- Volume
- 8
- Issue
- 19
- Pages
- 2282-2292
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1993063708
- Cited by
- 598
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Macleod, D., Charlton, J., Mullins, J., & Bird, A. P. (1994). Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes & Development. https://doi.org/10.1101/gad.8.19.2282
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